4.1 Therapeutic indications
Antepartum
- Induction of labour for medical reasons, e.g. in cases of post-term gestation, premature rupture of
the membranes, pregnancy-induced hypertension (pre-eclampsia).
- Stimulation of labour in hypotonic uterine inertia
- Syntocinon may also be indicated in early stage of pregnancy, as adjunctive therapy for
management of incomplete, inevitable or missed abortion.
Postpartum
- During caesarean section, but after the delivery of thechild.
- Prevention and treatment of postpartum haemorrhage related to uterineatony.

4.2 Posology and method of administration
Dosing
General target population
Induction or enhancement of labour
Syntocinon is given as an intravenous drip infusion or, preferably, by means of a variable-speed infusion pump.
For drip infusion it is recommended that 5 IU of Syntocinon be added to 500 ml of a physiological electrolyte
solution (such as sodium chloride 9 mg/ml). For patients in whom infusion of sodium chloride must is
contraindicated (see
section 4.4), 50 mg/ml dextrose solution may be used. To ensure even mixing, the bottle or bag must be turned
upside down several times before use.
The initial infusion rate should be set at 1 to 4 milliunits/minute (2 to 8 drops/minute). It may be increased
gradually at intervals not shorter than 20 minutes and increments of not more than 1–2 milliunits/minute until a
contraction pattern similar to that of normal labour is established. In pregnancy near term, this can often be
achieved with an infusion of less than 10 milliunits/minute (20 drops/minute), and the recommended maximum
rate is 20 milliunits/minute
(40 drops/minute). In the unusual event of higher rates being required, as may occur in the management of foetal
death in utero or for induction of labour at an earlier stage of pregnancy when the uterus is less sensitive to
oxytocin, it is advisable to use a more concentrated Syntocinon solution, e.g. 10 IU in 500 ml.
When using a motor-driven infusion pump which delivers smaller volumes than those given by drip infusion, the
concentration suitable for infusion within the recommended dosage range must be calculated according to the
specifications of the pump.
The frequency, strength and duration of contractions and also the fetal heart rate must be carefully monitored
throughout the infusion. Once an adequate level of uterine activity is attained, the infusion rate can often be
reduced. In the event of uterine hyperactivity and/or fetal distress, the infusion must be discontinued immediately.
If, in women who are at term or near term, regular contractions are not established after the infusion of a total
amount of 5 IU, it is recommended that the attempt to induce labour should be terminated; it may be repeated on
the following day, starting again from a rate of 1 to milliunits/minute.
Incomplete, inevitable, or missed abortion
5 IU by i.v. infusion (5 IU diluted in physiological electrolyte solution and administered as an i.v. drip infusion or,
preferably, by means of a variable-speed infusion pump over 5 minutes) or 5 IU to 10 IU i.m., followed by i.v.
infusion at a rate of 20 to 40 milliunits/minute, if necessary.
Caesarean section
5 IU by i.v. infusion (5 IU diluted in physiological electrolyte solution and administered as an i.v. drip infusion or,
preferably, by means of a variable-speed infusion pump over 5 minutes) immediately after delivery.
Prevention of postpartum uterine haemorrhage
The usual dose is 5 IU by i.v. infusion (5 IU diluted in physiological electrolyte solution and administered as an i.v.
drip infusion or, preferably, by means of a variable-speed infusion pump over 5 minutes) or 5 IU to 10 IU i.m. after
delivery of the placenta.
In women given Syntocinon for induction or enhancement of labour, the infusion should be continued at an
increased rate during the third stage of labour and for the next few hours thereafter.
Treatment of postpartum uterine haemorrhage
5 IU by i.v. infusion (5 IU diluted in physiological electrolyte solution and administered as an i.v. drip infusion or,
preferably, by means of a variable-speed infusion pump over 5 minutes), or 5 IU to 10 IU i.m., followed in severe
cases by intravenous infusion of a solution containing 5IU to 20 IU of oxytocin in 500 ml of an electrolytecontaining
diluent, run at the rate necessary to control uterine atony.
Special populations
Renal impairment
No studies have been performed in renally impaired patients.
Hepatic impairment
No studies have been performed in hepatically impaired patients.
Pediatric population
No studies have been performed in pediatric patients.
Geriatric patients
No studies have been performed in elderly patients (aged 65 years and over).

4.3 Contraindications  Hypersensitivity to the active substance or to any of the excipients, listed in section 6.1.  Hypertonic uterine contractions, foetal distress when delivery is not imminent. Any condition in which, for foetal or maternal reasons, spontaneous labour is unadvisable and/or vaginal delivery is contraindicated: e.g.:  cephalopelvic disproportion,  fetal malpresentation,  placenta praevia, vasa praevia,  placental abruption,  cord presentation or prolapse;  overdistension or impaired resistance of the uterus to rupture as in multiple pregnancy,  polyhydramnios,  grand multiparity and  in the presence of a uterine scar resulting from major surgery including classical caesarean section Syntocinon must not be administered within 6 hours after vaginal prostaglandins have been given (see section 4.5).

4.4 Special warnings and precautions for use
Induction of labour
The induction of labour by means of oxytocin should be attempted only when strictly indicated for medical reasons
rather than for convenience. Administration should only be under hospital conditions and qualified medical
supervision.
Syntocinon should not be used for prolonged periods in patients with oxytocin-resistant uterine inertia, severe preeclamptic
toxemia or severe cardiovascular disorders.
Syntocinon should not be given as i.v. bolus injection as it may cause an acute short-lasting hypotension
accompanied with flushing and reflex tachycardia.
Cardiovascular disorders
Syntocinon should be used with caution in patients who have a pre-disposition to myocardial ischemia due to
pre- existing cardiovascular disease (such as hypertrophic cardiomyopathy, valvular heart disease and/or
ischemic heart disease including coronary artery vasospasm), to avoid significant changes in blood pressure
and heart rate.
QT Syndrome
Syntocinon should be given with caution to patients with known ‘long QT syndrome’ or related symptoms and to
patients taking drugs that are known to prolong the QTc interval (see section 4.5).
When Syntocinon is given for induction and enhancement of labour:
- It must only be administered as an i.v. infusion, and never by s.c., i.m. or i.v. injection.
- Fetal distress and fetal death: Administration of oxytocin at excessive doses results in uterine overstimulation
which may cause foetal distress, asphyxia and death, or may lead to hypertonicity, tetanic contractions or
rupture of the uterus. Careful monitoring of foetal heart rate and uterine motility (frequency, strength, and
duration of contractions) is essential, so that the dosage may be adjusted to individual response.
- Particular caution is required in the presence of borderline cephalopelvic disproportion, secondary uterine
inertia, mild or moderate degrees of pregnancy-induced hypertension or cardiac disease and in patients above
35 years of age or with a history of lower-uterine-segment caesareansection.
- Disseminated intravascular coagulation: In rare circumstances, the pharmacological induction of labour
using uterotonic agents including oxytocin increases the risk of post partum disseminated intravascular
coagulation (DIC). The pharmacological induction itself and not a particular agent is linked to such risk.
This risk is increased in particular if the woman has additional risk factors for DIC such as being 35 years
of age or over, complications during the pregnancy and gestational age more than 40 weeks. In these
women, oxytocin or any other alternative drug should be used with care, and the practitioner should be
alerted by signs of DIC.
Intrauterine death
In the case of foetal death in utero, and/or in the presence of meconium-stained amniotic fluid, tumultuous labour
must be avoided, as it may cause amniotic fluid embolism.
Water intoxication
Because oxytocin possesses slight antidiuretic activity, its prolonged i.v. administration at high doses in conjunction
with large volumes of fluid (as may be the case in the treatment of inevitable or missed abortion, or in the
management of postpartum hemorrhage) may cause water intoxication associated with hyponatraemia. The
combined antidiuretic effect of oxytocin and the i.v. fluid administration may cause fluid overload leading to a
hemodynamic form of acute pulmonary edema without hyponatraemia. To avoid these rare complications, the
following precautions must be observed whenever high doses of oxytocin are administered over a long time: an
electrolyte-containing diluent must be used (not dextrose); the volume of infused fluid should be kept low (by
infusing oxytocin at a higher concentration than recommended for the induction or enhancement of labour at term);
fluid intake by mouth must be restricted; a fluid balance chart should be kept and serum electrolytes should be
measured when electrolyte imbalance is suspected.
Caution should be exercised in patients with severe renal impairment because of possible water intoxication and
possible accumulation of oxytocin (see section 5.1).
This medication contains small amounts of ethanol (alcohol), less than 100 mg per dose.
Anaphylaxis in women with latex allergy:
There have been reports of anaphylaxis following administration of oxytocin in women with a known latex
allergy. Due to the existing structural homology between oxytocin and latex, latex allergy/intolerance may be
an important predisposing risk factor for anaphylaxis following oxytocin administration.

4.5 Interaction with other medicinal products and other forms of interaction
Interaction resulting in a concomitant use not recommended
Prostaglandins and their analogues
Prostaglandins and their analogues facilitate contraction of the myometrium hence oxytocin can potentiate the uterine
action of prostaglandins and analogues and vice versa (see section 4.3).
Drugs prolonging the QT interval
Oxytocin should be considered as potentially arrhythmogenic, particularly in patients with other risk factors for torsades
de pointes such as drugs which prolong the QT interval or in patients with history of long QT syndrome (see section
4.4).
Interactions to be considered
Inhalation anesthetics
Inhalation anesthetics (e.g. cyclopropane, halothane, sevoflurane and desflurane) have a relaxing effect on uterus and
produce a notable inhibition of uterine tone and thereby, may diminish the uterotonic effect of oxytocin.
Vasoconstrictors/sympathomimetics
Oxytocin may enhance the vasopressor effects of vasoconstrictors and sympathomimetics, even those
contained in local anesthetics.
Caudal anesthetics
When given during or after caudal block anesthesia, oxytocin may potentiate the pressor effect of
sympathomimetic vasoconstrictor agents.

4.6 Fertility, Pregnancy and lactation
Women of childbearing potential
Not applicable for Syntocinon because of the nature of the indications.
Pregnancy
Pre-clinical data for oxytocin reveal no special hazard based on conventional studies of single dose acute
toxicity, genotoxicity, and mutagenicity. No standard teratogenicity and reproductive performance studies with
oxytocin are available (see section 5.3). Based on the wide experience with this drug and its chemical structure
and pharmacological properties, it is not expected to present a risk of fetal abnormalities when used as
indicated.
Breast-feeding
Oxytocin may be found in small quantities in mother’s breast milk. However, oxytocin is not expected to cause
harmful effects in the newborn because it passes into the alimentary tract where it undergoes rapid inactivation.
Fertility
Not applicable for Syntocinon because of the nature of the indications.

Not applicable.

Summary of the safety profile
When oxytocin is used by i.v. infusion for the induction or enhancement of labour, its administration at excessive
doses results in uterine overstimulation which may cause foetal distress, asphyxia and death, or may lead to
hypertonicity, tetanic contractions or rupture of the uterus.
Rapid i.v. bolus injection of oxytocin at doses amounting to several IU may result in acute short-lasting
hypotension accompanied with flushing and reflex tachycardia (see section 4.4). These rapid hemodynamic
changes may result in myocardial ischemia, particularly in patients with pre-existing cardiovascular disease.
Rapid i.v. bolus injection of oxytocin at doses amounting to several IU may also lead to QT prolongation.
In rare circumstances (i.e. incidence rate less than 0.0006), the pharmacological induction of labour using uterotonic
agents, including oxytocin, increases the risk of postpartum disseminated intravascular coagulation (see section 4.4).
Tabulated list of adverse reactions
The following adverse drug reactions have been reported regardless of the mode of administration:
Adverse reactions (Tables 1 and 2) are ranked under heading of frequency, using the following convention:
very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <
1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data.
Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. The
adverse reactions tabulated below are based on clinical trial results as well as postmarketing reports.
The adverse drug reactions that have been derived from post-marketing experience with Syntocinon are via
spontaneous case reports and literature cases. Because these reactions are reported voluntarily from a
population of uncertain size, it is not possible to reliably estimate their frequency which is therefore
categorized as not known.
Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ
class, adverse drug reactions are presented in order of decreasing seriousness.
Table 1 Adverse drug reactions in
mother Immune system disorders
Rare: anaphylactoid reaction associated with dyspnoea,
Hypotension or shock
Nervous system disorders
Common: headache
Cardiac disorders
Common: tachycardia, bradycardia
Uncommon: arrhythmia
Not known: myocardial ischemia, QTc prolongation
Vascular disorders
Not known: hypotension
Gastrointestinal disorders
Common: nausea, vomiting
Skin and subcutaneous tissue disorders
Rare: rash
Pregnancy, puerperium and perinatal conditions
Not known: uterine hypertonicity, tetanic contractions, rupture of the uterus
Metabolism and nutrition disorders
Not known: water intoxication, maternal hyponatraemia
Respiratory, thoracic and mediastinal disorders
Not known: acute pulmonary oedema
General disorders and administration site conditions
Not known: flushing
Blood and lymphatic system disorders
Not known: disseminated intravascular coagulation
Table 2 Adverse drug reactions in
fetus/neonate Pregnancy, puerperium and
perinatal conditions
Not known: foetal distress, asphyxia and death
Metabolism and nutrition
disorders
Not known: neonatal hyponatraemia
Description of selected adverse reactions
Water intoxication
Water intoxication associated with maternal and neonatal hyponatraemia has been reported in cases where high
doses of oxytocin have been administered together with large amounts of electrolyte-free fluid over a prolonged
period of time (see section 4.4).
The combined antidiuretic effect of oxytocin and the i.v. fluid administration may cause fluid overload leading to a
hemodynamic form of acute pulmonary edema without hyponatraemia (see section 4.4).

4.9 Overdose
The symptoms and consequences of overdose are those mentioned under section 4.4 Special warnings and
precautions for use and section 4.8 Undesirable effects. In addition, placental abruption and/or amniotic fluid
embolism as a result of uterine overstimulation have been reported.
Treatment
When signs or symptoms of overdose occur during i.v. administration of Syntocinon, the infusion must be
discontinued at once and oxygen should be given to the mother. In the event of water intoxication, it is essential to
restrict fluid intake, promote diuresis, correct electrolyte imbalance; and control possible convulsions.

5.1 Pharmacodynamic properties
- Pharmacotherapeutic group: Posterior pituitary lobe hormones, ATC code: H01B B02
-Mechanism of action & Pharmacodynamic effects:
Oxytocin is a cyclic nonapeptide that is obtained by chemical synthesis. This synthetic form is identical to the
natural hormone that is stored in the posterior pituitary and released into the systemic circulation in response to
suckling and labor. Oxytocin stimulates the smooth muscle of the uterus, more powerfully towards the end of
pregnancy, during
labor, and immediately postpartum. At these times, the oxytocin receptors in the myometrium are increased. The
oxytocin receptors are G-proteins coupled receptors. Activation of receptor by oxytocin triggers release of calcium
from intracellular stores and thus leads to myometrial contraction Oxytocin elicits rhythmic contractions in upper
segment of uterus, similar in frequency, force and duration to those observed during labor. Being synthetic,
oxytocin in Syntocinon does not contain vasopressin, But even in its pure form oxytocin possesses some weak
intrinsic vasopressin-like antidiuretic activity.
Based on in vitro studies, prolonged exposure of oxytocin causes desensitization of oxytocin receptors probably due
to down-regulation of oxytocin-binding sites, destabilization of oxytocin receptors mRNA and internalization of
oxytocin receptors.
Plasma levels and onset/duration of effect
Intravenous infusion: When Syntocinon is given by i.v. infusion at doses appropriate for induction or enhancement
of labor, the uterine response sets in gradually and usually reaches a steady state within 20 to 40 minutes. The
corresponding plasma levels of oxytocin are comparable to those measured during spontaneous first-stage labour.
Upon discontinuation of the infusion, or following a substantial reduction in the infusion rate, e.g. in the event of
overstimulation, uterine activity declines rapidly but may continue at an adequate lower level.
Intravenous injection and intramuscular injection: When administered by i.v. or i.m. injection for
prevention or treatment of postpartum hemorrhage, Syntocinon acts rapidly with a latency period of less than 1
minute by i.v. injection, and of 2 to 4 minutes by i.m. injection. The oxytocic response lasts for 30 to 60 minutes
after i.m. administration, possibly less after i.v. injection.

5.2 Pharmacokinetic properties
Oxytocin
Absorption
Oxytocin is rapidly absorbed from the i.m. site. Plasma levels of oxytocin following intravenous infusion
at 4 milliunits per minute in pregnant women at term were 2 to 5 microunits/ml.
Distribution
The steady-state volume of distribution determined in 6 healthy men after i.v. injection is 12.2 L or 0.17 L/kg.
Plasma protein binding is negligible for oxytocin. Oxytocin crosses the placenta in both directions. It may be
found in small quantities in mother’s breast milk.
Biotransformation
Oxytocinase is a glycoprotein aminopeptidase that is produced during pregnancy and appears in the plasma. It
is capable of degrading oxytocin. It is produced from both the mother and the fetus. Liver and kidney plays a
major role in metabolizing and clearing oxytocin from the plasma. Thus, liver, kidney and systemic circulation
contribute to the biotransformation of oxytocin.
Elimination
Plasma half life of oxytocin ranges from 3 to 20 minutes. The metabolites are excreted in urine whereas
lessthan 1% of the oxytocin is excreted unchanged in urine. The metabolic clearance rate amounts to 20
ml/kg/min in the pregnant woman.
Renal impairment
No studies have been performed in renally impaired patients. However considering the excretion of oxytocin
and its reduced excretion in urine due to anti-diuretic properties, the possible accumulation of oxytocin can
result in prolonged action of oxytocin.
Hepatic impairment
No studies have been performed in hepatically impaired patients. Pharmacokinetic alteration in patients with
impaired hepatic function is unlikely since metabolizing enzyme, oxytocinase, is not confined to liver alone and
the oxytocinase levels in placenta during the term has significantly increased. Therefore, biotransformation of
oxytocin in impaired hepatic function may not result in substantial changes in metabolic clearance of oxytocin
(see section 4.4).
Clinical studies
Syntocinon is an established product. No recent clinical studies are available.

5.3 Preclinical safety data
Pre-clinical data for oxytocin reveal no special hazard for humans based on studies of single dose acute
toxicity, genotoxicity, and mutagenicity.
Mutagenicity
An in vitro genotoxicity and mutagenicity study with oxytocin has been reported. Tests were negative for
chromosomal aberration and sister chromatid exchange in human peripheral lymphocyte cultures. No
significant changes in the mitotic index were noticed. Oxytocin had no genotoxic properties. The genotoxic
potential of oxytocin has not been determined in vivo.
Carcinogenicity, teratogenicity and reproduction toxicity
Treatment of rats with oxytocin in early pregnancy at doses considered sufficiently in excess of the
maximum recommended human dose caused embryonic loss in one study.
No standard teratogenicity, reproductive performance and carcinogenicity studies with oxytocin are available.

6.1 List of excipients
sodium acetate
trihydrate glacial
acetic acid
chlorobutanol
ethanol 94%
water for injections

In the absence of compatibility studies, Syntocinon must not be mixed with other medicinal products.

60 months

Store in a refrigerator (2 °C - 8 °C).

Package with 10 carton boxes, each comprising 10 colourless glass (type I) ampoules (10 x 10), each
containing 1 ml (5 IU/ml).
Package with 10 carton boxes, each comprising 10 colourless glass (type I) ampoules (10 x 10), each
containing 1 ml (10 IU/ml).

No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.